The limited proliferative potential of human diploid and other normal mammalian cells provides an excellent model for testing theories of in vitro and in vivo cellular aging. Many theories have been advanced to account for this phenomonon, but the proper experimental data have not been available to critically test these theories. We propose to determine the distributions of doubling potential am ng sets of subclones isolated at various times during the in vitro life-span of single clones of human diploid cells. Mathematical models corresponding to the various theories will be tested against the experimental life-span distributions. This method will allow us to evaluate many of the current theories and refine them or discard them as being possible explanations for aging in vitro.